title: The effect of tyrosine kinase inhibitor genistein on voltage-dependent K+ channels in rabbit coronary arterial smooth muscle cells.
abstract: We examined the effect of the protein tyrosine kinase (PTK) inhibitor, genistein on voltage-dependent K+ (Kv) channels in freshly isolated rabbit coronary arterial smooth muscle cells, using whole-cell patch clamp techniques. The amplitude of the Kv current was inhibited by genistein in a dose-dependent manner, with a Kd value of 7.51 microM. Genistein had no effect on the steady-state activation or inactivation of Kv channels. The applications of trains of pulses at 1 or 2 Hz caused a progressive increase in the genistein-blockade. Genistein produced use-dependent inhibition of the Kv currents, consistent with a slow recovery from inactivation in the presence of genistein. Daidzein and genistin, two inactive analogs of genistein, showed an inhibitory effect similar to that of genistein on Kv channels. Moreover, the absence of ATP inside the pipette did not influence the blocking effect of genistein. We suggest that genistein directly inhibited the Kv current, independently of PTK inhibition.
authors.affiliation: National Research Laboratory for Mitochondrial Signaling, FIRST Mitochondria Research Group, Department of Physiology and Biophysics, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea.
authors.forename: Eun A
authors.initials: EA
authors.lastname: Ko
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.forename: Youn Kyoung
authors.initials: YK
authors.lastname: Son
authors.forename: Do Hyung
authors.initials: DH
authors.lastname: Kim
authors.forename: Nari
authors.initials: N
authors.lastname: Kim
authors.forename: Hyoung Kyu
authors.initials: HK
authors.lastname: Kim
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Choi
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Jin
authors.initials: J
authors.lastname: Han
mesh_terms: D000818:Animals; D003331:Coronary Vessels / Q000166:cytology / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D019833:Genistein / Q000494:pharmacology*; D066298:In Vitro Techniques; D015640:Ion Channel Gating / Q000187:drug effects; D017136:Ion Transport / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011817:Rabbits
chemical_list: D024642:Potassium Channels, Voltage-Gated; D047428:Protein Kinase Inhibitors; D019833:Genistein; D011188:Potassium